Trimoprostil plasma concentration—gastric acid inhibition relationships: Potentiation by food

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Abstract
A single oral 1.5-mg dose of trimoprostil was taken before a standard meal and a matching placebo was taken after a standard meal by 10 subjects (group A). A 2nd group of 10 subjects took placebo before a meal and trimoprostil after the meal (group B), while a 3rd group took placebo both before and after the standard meal (group C). Food-stimulated gastric acid production was measured by intragastric titration for 6.5 h after dosing. Trimoprostil taken after the meal had a greater effect on gastric acid secretion than when taken before the meal. The duration of effect was 5-5.5 h in group B and 2-2.5 h in group A. Blood samples were drawn and assayed by gas chromatography-mass spectrometry for trimoprostil. Mean trimoprostil plasma concentration and mean inhibition of gastric acid secretion data were fit to 2 models by the Hill equation. The mean plasma concentration associated with 50% inhibition of gastric acid secretion was 1.25 ng/ml. Trimoprostil plasma concentrations between 3 and 4 ng/ml were associated with 70-80% gastric acid inhibition. There appears to be a pharmacokinetic-pharmacologic correlation between trimoprostil plasma concentrations and inhibition of gastric acid secretion. Trimoprostil (1.5 mg) in the presence of food appears to have a therapeutic advantage, in that it decreases acid secretion longer than when taken without food and suffers no loss of bioavailability.